Designed by iGEM: implemented by nature

I’ve been thinking recently about this year’s iGEM Jamboree, which is coming up soon. For those of you who don’t know, iGEM, the international Genetically Engineered Machines competition, challenges undergraduate students and high school students to make useful machines out of biological parts and implement them in living cells. The ideas are always interesting — usually somewhere between creative and wild, actually — and the Jamboree is where the different teams (165 of them this year) share their results, celebrate the new parts they’ve characterized, and generally have a good time. iGEM has turned out to be a major way for students from engineering and the quantitative sciences to get their first taste of biology.

iGEMmers are always on the lookout for biological modules that can be re-used for other purposes, and quorum sensing is something of a favorite. The system that produces bacterial gas vesicles that allow bacteria to float also seems to be ripe for re-engineering. And so a recent paper that identifies a gas vesicle system controlled by quorum sensing caught my eye (Ramsay et al. 2011. A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium. PNAS doi:10.1073/pnas.1109169108). Ooh, I thought — that looks interesting. You could target bacteria to something you want to float up — the Titanic, say — and turn on the gas vesicles when you have enough bacteria. And indeed, it’s a natural iGEM project; so much so, that the 2008 Kyoto team already tried to do it. They did not, in fact, raise the Titanic, but they did show [pdf] that their engineered bacteria could move a ~10µm bead. One must start somewhere.

Many bacteria produce gas vesicles to regulate their buoyancy, but we don’t know all that much about how the production of these vesicles is regulated. Ramsay et al.’s paper is the first to show that quorum sensing can control the production of these vesicles in nature. Changes in the availability of light or oxygen have also been shown to increase vesicle production in some cases. Thus, it’s thought that the vesicle-producing cells may turn up the gas when they find themselves drifting too far away from the air-water interface. It’s an alternative to turning on flagellum formation (which would allow swimming towards the surface), and under some circumstances appears to be a more energetically favorable option.

Ramsay et al. noticed some morphological features (opaque colonies of bacteria) that led them to suspect that a bacterial strain they’d been working on, strain #39006 of an opportunistic pathogen called Serratia, might express gas vesicles. They used a genetic screen to identify a set of genes homologous to the gas vesicle-producing genes in other bacteria. Unusually, Serratia 39006 expresses three different variants of the main protein used to make the vesicles, called GvpA; electron microscopy revealed that these bacteria also contain gas vesicles of several different diameters, perhaps built of different GvpA variants, or mixtures of the different variants. And yes, the expression of the vesicles causes the bacteria to float; the resemblance between these proteins and the previously identified gas vesicle proteins is not a coincidence. Porting the relevant genes to E. coli also produced floating E. coli colonies.

The authors found that the gas vesicles were produced at a late stage in Serratia cultures, suggesting the possibility that the expression of gas vesicle proteins might be controlled by quorum sensing signals. Serratia manages many other functions via quorum sensing, including virulence; it uses a chemical signal, butanoyl-homoserine lactone, to monitor how dense its population has become, and a small RNA-binding protein, RmsA, as a quorum-dependent post-transcriptional regulator of several genes. For example, the authors have previously shown that RmsA represses the production of flagellar genes; and it now turns out that RmsA is required for the expression of the gas vesicle proteins. So, it appears that Serratia makes an either-or choice between swimming and floating, depending on its population size. This might make sense for a couple of different reasons. Because swimming and floating are both mechanisms for getting away from wherever you currently are, it seems reasonable that you wouldn’t want to activate them both at once. Large mats of bacteria would be expected to float better than individual cells, perhaps explaining why high density activates floating at the expense of swimming; floating at high cell density may also allow you to suffocate your competitors. Swimming may be a better bet when the population is small but nutrients are nevertheless limiting, meaning that each individual needs to be able to head in a different direction. In any case, it appears that nature has anticipated the need to create controllable biological flotation devices, so now it’s just a question of harnessing the numbers required. The Kyoto team calculated that a mere 5 x 10(16) of the bacteria they designed would be sufficient to lift the 40,000 tons of the Titanic. Easy peasy lemon squeezy.

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§ 3 Responses to Designed by iGEM: implemented by nature

This year, the Harvard iGEM team is using technologies pioneered by the Church lab to explore new zinc finger motifs. The genomic engineering is a great foundational technology for iGEM. They’ll be going to regionals in October and the finals, if they do well, will be at MIT in early November.

Nice to see the interest in the paper! As George S. often says, “if you can think of a bacterium doing something, it’s probably already happened”
Am happy to answer any questions.
Josh Ramsay, (author of the paper).